Background-To prospectively apply an automated, quantitative 3-D approach to imaging and airway analysis to assess airway remodeling in asthma.

IntroductionObstructive sleep apnea (OSA) patients show hippocampal-related autonomic and neurological symptoms, including impaired memory and depression, which differ by sex, and are mediated in distinct hippocampal subfields. Determining sites and extent of hippocampal sub-regional injury in OSA could reveal localized structural damage linked with OSA symptoms.MethodsHigh-resolution T1-weighted images were collected from 66 newly-diagnosed, untreated OSA (mean age ± SD: 46.3 ± 8.8 years; mean AHI ± SD: 34.1 ± 21.5 events/h;50 male) and 59 healthy age-matched control (46.8 ± 9.0 years;38 male) participants. We added age-matched controls with T1-weighted scans from two datasets (IXI, OASIS-MRI), for 979 controls total (426 male/46.5 ± 9.9 years). We segmented the hippocampus and analyzed surface structure with “FSL FIRST” software, scaling volumes for brain size, and evaluated group differences with ANCOVA (covariates: total-intracranial-volume, sex; P < .05, corrected).ResultsIn OSA relative to controls, the hippocampus showed small areas larger volume bilaterally in CA1 (surface displacement ≤0.56 mm), subiculum, and uncus, and smaller volume in right posterior CA3/dentate (≥ − 0.23 mm). OSA vs. control males showed higher bilateral volume (≤0.61 mm) throughout CA1 and subiculum, extending to head and tail, with greater right-sided increases; lower bilateral volumes (≥ − 0.45 mm) appeared in mid- and posterior-CA3/dentate. OSA vs control females showed only right-sided effects, with increased CA1 and subiculum/uncus volumes (≤0.67 mm), and decreased posterior CA3/dentate volumes (≥ − 0.52 mm). Unlike males, OSA females showed volume decreases in the right hippocampus head and tail.ConclusionsThe hippocampus shows lateralized and sex-specific, OSA-related regional volume differences, which may contribute to sex-related expression of symptoms in the sleep disorder. Volume increases suggest inflammation and glial activation, whereas volume decreases suggest long-lasting neuronal injury; both processes may contribute to dysfunction in OSA.

IntroductionBrain structural injury and metabolic deficits in the hippocampus and caudate nuclei may contribute to cognitive and emotional deficits found in obstructive sleep apnea (OSA) patients. If such contributions exist, resting‐state interactions of these subcortical sites with cortical areas mediating affective symptoms and cognition should be disturbed. Our aim was to examine resting‐state functional connectivity (FC) of the hippocampus and caudate to other brain areas in OSA relative to control subjects, and to relate these changes to mood and neuropsychological scores.MethodsWe acquired resting‐state functional magnetic resonance imaging (fMRI) data from 70 OSA and 89 healthy controls using a 3.0‐Tesla magnetic resonance imaging scanner, and assessed psychological and behavioral functions, as well as sleep issues. After standard fMRI data preprocessing, FC maps were generated for bilateral hippocampi and caudate nuclei, and compared between groups (ANCOVA; covariates, age and gender).ResultsObstructive sleep apnea subjects showed significantly higher levels of anxiety and depressive symptoms over healthy controls. In OSA subjects, the hippocampus showed disrupted FC with the thalamus, para‐hippocampal gyrus, medial and superior temporal gyrus, insula, and posterior cingulate cortex. Left and right caudate nuclei showed impaired FC with the bilateral inferior frontal gyrus and right angular gyrus. In addition, altered limbic‐striatal‐cortical FC in OSA showed relationships with behavioral and neuropsychological variables.ConclusionsThe compromised hippocampal‐cortical FC in OSA may underlie depression and anxious mood levels in OSA, while impaired caudate‐cortical FC may indicate deficits in reward processing and cognition. These findings provide insights into the neural mechanisms underlying the comorbidity of mood and cognitive deficits in OSA.

Summary The insular cortex is injured in obstructive sleep apnea (OSA), and responds inappropriately to autonomic challenges, suggesting neural reorganization. The objective was to assess whether the neural changes result from γ-aminobutyric acid (GABA) and glutamate alterations. We studied 14 OSA patients (mean age±SD: 47.5±10.5 years; 9 male; AHI:29.5±15.6 events/hour) and 22 healthy participants (47.5±10.1 years;11 male), using magnetic resonance spectroscopy to detect GABA and glutamate levels in insular cortices. We localized the cortices with anatomical scans, and measured neurochemical levels from anterior-to-mid regions. Left and right anterior insular cortices showed lower GABA and higher glutamate in OSA vs. healthy subjects (GABA Left:OSA N=6: 0.36±0.10 [mean±std], healthy N=5:0.62±0.18 p<0.05), Right:OSA N=11:0.27±0.09, healthy N=14:0.45±0.16; p<0.05; glutamate Left:OSA N=6:1.61±0.32, healthy N=8:0.94±0.34; p<0.05, Right:OSA N=14:1.26±0.28, healthy N=19:1.02±0.28; p<0.05). GABA and glutamate levels were correlated only within the healthy group in the left insula (r=−0.9, p<0.05). The altered anterior insular levels of GABA and glutamate may modify integration and projections to autonomic areas, contributing to the impaired cardiovascular regulation in OSA.

Asthma is a chronic inflammatory disease that affects both the large and small airways and results in bronchoconstriction, mucous hypersecretion, smooth muscle hypertrophy, and subepithelial fibrosis. To gain insight into the pathophysiology of asthma, chest computed tomography (CT) has been investigated as a noninvasive method to evaluate airway wall thickness of medium and large airways. Hyperpolarized gas MRI can assess the functional alterations of airflow within the lung resulting from the structural changes in the airways. In this article, we review the application of CT-based techniques and hyperpolarized gas MRI to study structural and functional changes in asthma. From the result of studies with CT and hyperpolarized gas MRI, it is becoming apparent that asthma has a regional distribution within the lung, that is, some areas of the lung are more affected than others. Furthermore, there appears to be some persistence to this distribution which may explain the observed patterns of airway remodeling and provide targets for localized therapies such as local application of anti-inflammatory agents or bronchial thermoplasty. Thus, cross sectional imaging in asthma is providing new insights into the pathophysiology of the disease and has the potential to become essential in the guidance of localized treatments.